| 1. |
- Johansson, Karl-Axel, et al.
(författare)
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The quality assurance process for the ARTSCAN head and neck study - a practical interactive approach for QA in 3DCRT and IMRT.
- 2008
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 87:2, s. 290-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
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| 2. |
- Svensson, Johan, 1964, et al.
(författare)
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Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:6, s. 2028-33
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.
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| 3. |
- Wernstedt, Ingrid, 1978, et al.
(författare)
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A common polymorphism in the interleukin-6 gene promoter is associated with overweight
- 2004
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Ingår i: Int J Obes Relat Metab Disord. ; 28:10, s. 1272-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74). MEASUREMENTS: Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
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| 4. |
- Wiklund, Lars, 1954, et al.
(författare)
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Neurogenetik.
- 2006
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Ingår i: Neurologi. Fagius J och Aquilonius S-M (ed.). - Stockholm : Liber. - 9789147053131
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Astengo, Marco, et al.
(författare)
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Physical training after percutaneous coronary intervention in patients with stable angina: effects on working capacity, metabolism, and markers of inflammation
- 2010
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267. ; 17:3, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- Objective Physical activity is effective in primary and secondary prevention of cardiovascular disease. In this study, we tested the hypothesis that exercise training improves glucose and lipid metabolism, the inflammatory/anti-inflammatory balance, and the outcome of elective percutaneous coronary intervention (PCI) in patients with stable coronary disease. Methods Sixty-two patients scheduled to undergo PCI for stable angina were randomized to intensive physical activity (n = 33) consisting of home-based exercise on a bicycle ergometer or maintain their usual sedentary life (n = 29). The training program started 2 months before PCI and terminated 6 months afterwards. Clinical examination, blood sampling (fasting glucose, glycated hemoglobin, lipid profile, apolipoprotein B, apolipoprotein A1, C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, and interleukin-10), and maximal exercise tests were performed at inclusion, 1 week before PCI, and 3 and 6 months afterwards. Results Fifty-six patients [28 per group, 45 men, mean age 63 (SD 7.8) years] completed the follow-up. According to self-reports, patients in the training group exercised more often and longer [4.9 (SD 1.1) vs. 0.6 (SD 1.3) days/week, 36 (SD 12) vs. 15 (SD 31) min/session, P <0.0001]. Improvement in maximal exercise capacity was significantly better in the training group [27 (SD 27) vs. 9 (SD 27)W, P = 0.02]. Exercise had no significant effects on glucose and lipid metabolism, plasma cytokines, or acute-phase reactants. Conclusion A home-based training program significantly improved maximal exercise capacity but did not affect glucose or lipid metabolism or markers of inflammation. Eur J Cardiovasc Prev Rehabil 17:349-354 © 2010 The European Society of Cardiology
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| 6. |
- Borén, Jan, 1963, et al.
(författare)
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Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel.
- 2017
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 38:32, s. 2459-2472
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Tidskriftsartikel (refereegranskat)abstract
- To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.
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| 7. |
- Borén, Jan, 1963, et al.
(författare)
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New prospects for PCSK9 inhibition?
- 2018
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 39:27, s. 2600-2601
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Boström, Pontus, 1982, et al.
(författare)
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Hypoxia converts human macrophages into triglyceride-loaded foam cells.
- 2006
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 26:8, s. 1871-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerotic lesions have regions that are hypoxic. Because the lesion contains macrophages that are loaded with lipid, we investigated whether hypoxia can influence the accumulation of lipids in these cells. METHODS AND RESULTS: Exposure of human macrophages to hypoxia for 24 hours resulted in an increased formation of cytosolic lipid droplets and an increased accumulation of triglycerides. Exposure of the macrophages to oxidized low-density lipoprotein (oxLDL) increased the accumulation of cytosolic lipid droplets because of an increase in cellular cholesterol esters. The accumulation of lipid droplets in oxLDL-treated cells was further increased after hypoxia, caused by an increased level of triglycerides. Expression analyses combined with immunoblot or RT-PCR demonstrated that hypoxia increased the expression of several genes that could promote the accumulation of lipid droplets. Hypoxia increased the mRNA and protein levels of adipocyte differentiation-related protein (ADRP). It is well known that an increased expression of ADRP increases the formation of lipid droplets. Hypoxia decreased the expression of enzymes involved in beta-oxidation (acyl-coenzyme A synthetase and acyl-coenzyme A dehydrogenase) and increased the expression of stearoyl-coenzyme A desaturase, an important enzyme in the fatty acid biosynthesis. Moreover, exposure to hypoxia decreased the rate of beta-oxidation, whereas the accumulation of triglycerides increased. CONCLUSIONS: The results demonstrate that exposure of human macrophages to hypoxia causes an accumulation of triglyceride-containing cytosolic lipid droplets. This indicates that the hypoxia present in atherosclerotic lesions can contribute to the formation of the lipid-loaded macrophages that characterize the lesion and to the accumulation of triglycerides in such lesions.
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| 9. |
- Brown, David A, et al.
(författare)
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Macrophage inhibitory cytokine 1 : a new prognostic marker in prostate cancer.
- 2009
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 15:21, s. 6658-6664
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: High serum levels of macrophage inhibitory cytokine 1 (MIC-1) are strongly associated with metastatic prostate cancer, suggesting MIC-1 is a biomarker for prostate cancer prognosis. EXPERIMENTAL DESIGN: We conducted a prospective cohort study of 1,442 Swedish men with a pathologically verified diagnosis of prostate cancer between 2001 and 2003. Blood was drawn either pretreatment (n = 431) or posttreatment (n = 1,011) and cases were followed for a mean time of 4.9 years (range, 0.1-6.8 years). RESULTS: MIC-1 serum levels independently predicted poor cancer-specific survival with an almost 3-fold higher cancer death rate in patients with serum levels in the highest quartile compared with men with serum levels in the lowest quartile (adjusted hazard ratio, 2.98; 95% confidence interval, 1.82-4.68). Pretreatment MIC-1 levels revealed an even stronger association with disease outcome with an 8-fold higher death rate in the highest compared with the lowest category (adjusted hazard ratio, 7.98; 95% confidence interval, 1.73-36.86). Among patients considered to have localized disease, MIC-1 significantly increased the discriminative capacity between indolent and lethal prostate cancer compared with the established prognostic markers clinical stage, pathologic grade, and prostate-specific antigen level (P = 0.016). A sequence variant in the MIC-1 gene was associated with decreased MIC-1 serum levels (P = 0.002) and decreased prostate cancer mortality (P = 0.003), suggesting a causative role of MIC-1 in prostate cancer prognosis. CONCLUSIONS: Serum MIC-1 concentration is a novel biomarker capable of predicting prostate cancer prognosis.
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| 10. |
- Catapano, A. L., et al.
(författare)
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Think Again About Cholesterol Survey
- 2015
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Ingår i: Atherosclerosis Supplements. - : Elsevier BV. - 1567-5688. ; 20, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular disease (CVD) is still the main cause of death in Europe. Elevated plasma cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), is the main causative risk factor for CVD, most prominently associated with coronary heart disease. A widespread disinformation about cholesterol and CVD is one factor underlying a poor compliance to lipid-lowering therapy. To investigate how cholesterol, CVD and cholesterol reduction is perceived in the population, a survey was commissioned by the European Atherosclerosis Society (EAS). Nearly half of people above 25 years of age are most worried about cancer (45%), compared to just over one in four who are worried about heart disease (27%). A majority believe being overweight (72%), blood pressure (70%) and smoking (67%) most affect heart health, far more than note cholesterol (59%) and family history (39%). The majority of adults recognize that high LDL (or "bad") cholesterol should be a health priority for everyone, including those younger than 40 and those who are not overweight. However, 1 in 4 (25%) incorrectly believe that it does not need to be a concern until someone shows signs or symptoms. Although 89% of adults surveyed agreed it is important for people to know whether or not they have high LDL-C, an overwhelming 92% did not know their LDL-C levels or had never had their cholesterol levels tested. A high 63% had never heard of familial hypercholesterolemia: France had the lowest level of awareness (41%) to Denmark with a high 80%, and the association of the disease with high levels of LDL-C is quite poor (only 36%), with Sweden only at 22% versus a high in Spain of 54%. A large part of the people participating in the survey were quite uncertain about the modality of transmission for familial hypercholesterolemia in the family. All in all, this survey highlights the need for more information among citizens for the role of cholesterol in determining CVD.
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